Evidence for a new type of PGE1 receptor coupled to cGMP accumulation was obtained. Cell lines with PGE1 receptors coupled only to cAMP were found as well as cell lines with 2 species of PGE1 receptors, one coupled to cAMP accumulation, the other to cGMP accumulation. The 2 species of PGE1 receptors also desensitize at different rates. These results show that the coupling of PGE1 to increases in cAMP and cGMP levels are clonally inherited properties which can be expressed independently.